The invention relates to nucleic acid molecules, proteins encoded by such nucleic acid molecules; and use of the proteins and nucleic acid molecules.
Kallikreins are a group of serine proteases that are found in diverse tissues and biological fluids. The term “kallikrein” was first introduced by Werle and colleagues who found high levels of their original isolates in the pancreas (in Greek, the “kallikreas”) (1,2). Kallikreins are divided into two main groups; the plasma kallikrein, which is a single gene (3), and the tissue kallikreins, which are encoded by a large multi-gene family in rodents (4,5). Until recently, the human kallikrein gene family was thought to consist of only three members (6). However, 11 new members of the kallikrein gene family have been identified (7-18). The progress in this area of investigation has recently been reviewed (7).
Prostate specific antigen (PSA), currently the most useful tumor marker for prostate cancer diagnosis and monitoring, is a member of the human kallikrein gene family of serine proteases (19,20). In addition to PSA, human glandular kallikrein 2 (hK2, encoded by the KLK2 gene) has been proposed as an adjuvant diagnostic marker for prostate cancer (21,22). Moreover, accumulating evidence indicates that other members of the expanded kallikrein gene family may be associated with malignancy (7). The normal epithelial cell-specific 1 gene (NES1) (KLK10, according to the approved human tissue kallikrein gene nomenclature) was found to be a novel tumor suppressor, which is down-regulated during breast cancer progression (23). Other gene family members, including zyme (KLK6), neuropsin (KLK8), and human stratum corneum chymotyrptic enzyme (HSCCE; KLK7) were also found to be differentially expressed in certain types of malignancies (24-26).